The modulation of adult neuroplasticity is involved in the mood-improving actions of atypical antipsychotics in an animal model of depression
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/49607 |
Resumo: | Depression is a prevalent psychiatric disorder with an increasing impact in global public health. However, a large proportion of patients treated with currently available antidepressant drugs fail to achieve remission. Recently, antipsychotic drugs have received approval for the treatment of antidepressant-resistant forms of major depression. The modulation of adult neuroplasticity, namely hippocampal neurogenesis and neuronal remodeling, has been considered to have a key role in the therapeutic effects of antidepressants. However, the impact of antipsychotic drugs on these neuroplastic mechanisms remains largely unexplored. In this study, an unpredictable chronic mild stress protocol was used to induce a depressive-like phenotype in rats. In the last 3 weeks of stress exposure, animals were treated with two different antipsychotics: haloperidol (a classical antipsychotic) and clozapine (an atypical antipsychotic). We demonstrated that clozapine improved both measures of depressive-like behavior (behavior despair and anhedonia), whereas haloperidol aggravated learned helplessness in the forced-swimming test and behavior flexibility in a cognitive task. Importantly, an upregulation of adult neurogenesis and neuronal survival was observed in animals treated with clozapine, whereas haloperidol promoted a downregulation of these processes. Furthermore, clozapine was able to re-establish the stress-induced impairments in neuronal structure and gene expression in the hippocampus and prefrontal cortex. These results demonstrate the modulation of adult neuroplasticity by antipsychotics in an animal model of depression, revealing that the atypical antipsychotic drug clozapine reverts the behavioral effects of chronic stress by improving adult neurogenesis, cell survival and neuronal reorganization. |
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The modulation of adult neuroplasticity is involved in the mood-improving actions of atypical antipsychotics in an animal model of depressionCiências Médicas::Medicina BásicaScience & TechnologyDepression is a prevalent psychiatric disorder with an increasing impact in global public health. However, a large proportion of patients treated with currently available antidepressant drugs fail to achieve remission. Recently, antipsychotic drugs have received approval for the treatment of antidepressant-resistant forms of major depression. The modulation of adult neuroplasticity, namely hippocampal neurogenesis and neuronal remodeling, has been considered to have a key role in the therapeutic effects of antidepressants. However, the impact of antipsychotic drugs on these neuroplastic mechanisms remains largely unexplored. In this study, an unpredictable chronic mild stress protocol was used to induce a depressive-like phenotype in rats. In the last 3 weeks of stress exposure, animals were treated with two different antipsychotics: haloperidol (a classical antipsychotic) and clozapine (an atypical antipsychotic). We demonstrated that clozapine improved both measures of depressive-like behavior (behavior despair and anhedonia), whereas haloperidol aggravated learned helplessness in the forced-swimming test and behavior flexibility in a cognitive task. Importantly, an upregulation of adult neurogenesis and neuronal survival was observed in animals treated with clozapine, whereas haloperidol promoted a downregulation of these processes. Furthermore, clozapine was able to re-establish the stress-induced impairments in neuronal structure and gene expression in the hippocampus and prefrontal cortex. These results demonstrate the modulation of adult neuroplasticity by antipsychotics in an animal model of depression, revealing that the atypical antipsychotic drug clozapine reverts the behavioral effects of chronic stress by improving adult neurogenesis, cell survival and neuronal reorganization.This work was co-funded by the Life and Health Sciences Research Institute (ICVS), and Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (Projects NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023). This work has been also funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE) and by National funds, through the FCT, under the scope of the project POCI-01-0145-FEDER-007038. We thank Luís Martins and Ana Lima for the technical assistanceinfo:eu-repo/semantics/publishedVersionNature Publishing GroupUniversidade do MinhoMorais, Mónica Susana DiasPatrício, Patrícia CarvalhoPinheiro, António Maria Restolho MateusAlves, Nuno Dinis Lopes OliveiraSantos, Ana Rita Machado dosCorreia, Joana Sofia SilvaPereira, J.Pinto, LuísaSousa, NunoPeixoto, João Miguel Seiça Bessa2017-06-022017-06-02T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/49607engMorais, M., Patrício, P., Mateus-Pinheiro, A., Alves, N. D., Machado-Santos, A. R., Correia, J. S., ... & Bessa, J. M. (2017). The modulation of adult neuroplasticity is involved in the mood-improving actions of atypical antipsychotics in an animal model of depression. Translational Psychiatry, 7(6), e11461662-515310.1038/tp.2017.12028585931https://www.nature.com/articles/tp2017120info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:27:38Zoai:repositorium.sdum.uminho.pt:1822/49607Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:22:17.361369Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
The modulation of adult neuroplasticity is involved in the mood-improving actions of atypical antipsychotics in an animal model of depression |
title |
The modulation of adult neuroplasticity is involved in the mood-improving actions of atypical antipsychotics in an animal model of depression |
spellingShingle |
The modulation of adult neuroplasticity is involved in the mood-improving actions of atypical antipsychotics in an animal model of depression Morais, Mónica Susana Dias Ciências Médicas::Medicina Básica Science & Technology |
title_short |
The modulation of adult neuroplasticity is involved in the mood-improving actions of atypical antipsychotics in an animal model of depression |
title_full |
The modulation of adult neuroplasticity is involved in the mood-improving actions of atypical antipsychotics in an animal model of depression |
title_fullStr |
The modulation of adult neuroplasticity is involved in the mood-improving actions of atypical antipsychotics in an animal model of depression |
title_full_unstemmed |
The modulation of adult neuroplasticity is involved in the mood-improving actions of atypical antipsychotics in an animal model of depression |
title_sort |
The modulation of adult neuroplasticity is involved in the mood-improving actions of atypical antipsychotics in an animal model of depression |
author |
Morais, Mónica Susana Dias |
author_facet |
Morais, Mónica Susana Dias Patrício, Patrícia Carvalho Pinheiro, António Maria Restolho Mateus Alves, Nuno Dinis Lopes Oliveira Santos, Ana Rita Machado dos Correia, Joana Sofia Silva Pereira, J. Pinto, Luísa Sousa, Nuno Peixoto, João Miguel Seiça Bessa |
author_role |
author |
author2 |
Patrício, Patrícia Carvalho Pinheiro, António Maria Restolho Mateus Alves, Nuno Dinis Lopes Oliveira Santos, Ana Rita Machado dos Correia, Joana Sofia Silva Pereira, J. Pinto, Luísa Sousa, Nuno Peixoto, João Miguel Seiça Bessa |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Morais, Mónica Susana Dias Patrício, Patrícia Carvalho Pinheiro, António Maria Restolho Mateus Alves, Nuno Dinis Lopes Oliveira Santos, Ana Rita Machado dos Correia, Joana Sofia Silva Pereira, J. Pinto, Luísa Sousa, Nuno Peixoto, João Miguel Seiça Bessa |
dc.subject.por.fl_str_mv |
Ciências Médicas::Medicina Básica Science & Technology |
topic |
Ciências Médicas::Medicina Básica Science & Technology |
description |
Depression is a prevalent psychiatric disorder with an increasing impact in global public health. However, a large proportion of patients treated with currently available antidepressant drugs fail to achieve remission. Recently, antipsychotic drugs have received approval for the treatment of antidepressant-resistant forms of major depression. The modulation of adult neuroplasticity, namely hippocampal neurogenesis and neuronal remodeling, has been considered to have a key role in the therapeutic effects of antidepressants. However, the impact of antipsychotic drugs on these neuroplastic mechanisms remains largely unexplored. In this study, an unpredictable chronic mild stress protocol was used to induce a depressive-like phenotype in rats. In the last 3 weeks of stress exposure, animals were treated with two different antipsychotics: haloperidol (a classical antipsychotic) and clozapine (an atypical antipsychotic). We demonstrated that clozapine improved both measures of depressive-like behavior (behavior despair and anhedonia), whereas haloperidol aggravated learned helplessness in the forced-swimming test and behavior flexibility in a cognitive task. Importantly, an upregulation of adult neurogenesis and neuronal survival was observed in animals treated with clozapine, whereas haloperidol promoted a downregulation of these processes. Furthermore, clozapine was able to re-establish the stress-induced impairments in neuronal structure and gene expression in the hippocampus and prefrontal cortex. These results demonstrate the modulation of adult neuroplasticity by antipsychotics in an animal model of depression, revealing that the atypical antipsychotic drug clozapine reverts the behavioral effects of chronic stress by improving adult neurogenesis, cell survival and neuronal reorganization. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-06-02 2017-06-02T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/49607 |
url |
http://hdl.handle.net/1822/49607 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Morais, M., Patrício, P., Mateus-Pinheiro, A., Alves, N. D., Machado-Santos, A. R., Correia, J. S., ... & Bessa, J. M. (2017). The modulation of adult neuroplasticity is involved in the mood-improving actions of atypical antipsychotics in an animal model of depression. Translational Psychiatry, 7(6), e1146 1662-5153 10.1038/tp.2017.120 28585931 https://www.nature.com/articles/tp2017120 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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